HIV antibodies. Antigen modification regulates competition of broad and narrow neutralizing HIV antibodies.

HIV antibodies. Antigen modification regulates competition of broad and narrow neutralizing HIV antibodies.
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DOI:
10.1126/science.1259206
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发表时间:
2014-12-12
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Stamatatos L
Stamatatos L
中科院分区:
其他
文献类型:
--
作者:
McGuire AT;Dreyer AM;Carbonetti S;Lippy A;Glenn J;Scheid JF;Mouquet H;Stamatatos L

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一些艾滋病毒感染者会产生广泛中和抗体(bNAb),而大多数人会产生仅中和少数病毒的抗体(nNAb)。bNAb,而不是nNAb,保护动物免受实验感染,可能是有效疫苗的关键组成部分。nNAb和bNAb靶向病毒包膜糖蛋白(Env)的相同区域,但由于仍不清楚的原因,Env免疫仅引发nNAb。我们表明,与种系回复(gl)bNAbs相反,glnNAbs识别不同的重组Envs。此外,由于结合亲和力的差异,与bNA B B细胞祖细胞相比,nNA B B细胞祖细胞在活化和内化Env方面具有优势。然后,我们确定了一种Env修饰策略,该策略使靶向与bNAb的表位重叠的表位的nNA B B细胞的活化最小化。
Some HIV-infected individuals develop broadly neutralizing antibodies (bNAbs), whereas most develop antibodies that neutralize only a narrow range of viruses (nNAbs). bNAbs, but not nNAbs, protect animals from experimental infection and are likely a key component of an effective vaccine. nNAbs and bNAbs target the same regions of the viral envelope glycoprotein (Env), but for reasons that remain unclear only nNAbs are elicited by Env immunization. We show that in contrast to germline-reverted (gl) bNAbs, glnNAbs recognized diverse recombinant Envs. Moreover, owing to binding affinity differences, nNAb B cell progenitors had an advantage in becoming activated and internalizing Env compared with bNAb B cell progenitors. We then identified an Env modification strategy that minimized the activation of nNAb B cells targeting epitopes that overlap those of bNAbs.
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